1. Wear particle mediated osteolysis - We have clearly established that osteoprogenitor cells represent one of the target cell types dramatically affected by the presence of wear debris particles derived from metallic orthopaedic implant materials. Particle treated adult stem cells slow down in their proliferation, are induced to undergo apoptosis, and are inhibited in osteogenic differentiation. Our recent study demonstrated that particle osteolysis and accompanying disruption of cytoskeletal architecture and cell adhesion, as well as the release of specific cytokines, are responsible for the titanium particle effects on mesenchymal stem cells. 2. Molecular detection of orthopaedic infections - We have developed polymerase chain reaction (PCR)-based technologies for the detection of bacterial infection in orthopaedically relevant tissues, specifically septic arthritis and periprosthetic infection. By targeting RNA, both mRNA and rRNA, we are able to use quantitative reverse transcription-PCR (qRT-PCR) to detect as well as assess the viable bacterial load. A clinical series utilizing synovial fluid has been completd demonstrating potential clinical application of the technology. 3. Supraphysiological impact mediated cartilage degeneration model - We have developed a reproducible, spring-loaded impactor based rabbit model to study impact-induced articular degeneration. We are focusing on the analysis of early cellular responses that lead to subsequent osteoarthritis-like articular cartilage degeneration. 4. Animal model of distraction osteogenesis - A unique and effective procedure to induce postnatal bone growth, the mechanism of distraction osteogenesis is not well understood. We have developed and completed a study of a mouse model to analyze by microarray technology the gene expression events accomanying distraction osteogenesis. In addition, we are developing an in vitro mechanical activation model using culture cells in 2-D and 3-D conditions to simulate distraction osteogenesis.